The goal of the proposed research is to study the effects of acutely administered barbiturates, which are prototypic sedative-hypnotic drugs of abuse, on three types of inhibitory pathways in the spinal cord reflex system (direct, presynaptic, and recurrent inhibition). These same reflexes were studied previously in physically dependent animals. All three types of inhibition were decreased at some time during the withdrawal syndrome, leading to an hypothesis to explain barbiturate dependence. It was thought that the nervous system might adapt during chronic treatment by decreasing function in inhibitory systems. That would leave excitatory pathways unbalanced and the overall output of the nervous system would be greater than expected (tolerance). After stopping drug intake, this imbalance between excitation and inhibition would be fully unmasked and withdrawal hyperexcitability would be produced until inhibitory systems could again return to a normal level of function. If this is true, decreased inhibitory function should be demonstrable in physically dependent animals before the onset of overt withdrawal signs. Previous experiments included data taken from animals before the onset of withdrawal signs. However, the data were not immediately useful because the results were a synthesis of two factors; changes in inhibitory function due to physical dependence, and the direct effect of residual pentobarbital remaining in the circulation after the last dose of chronic treatment. To determine what part of the altered inhibitory function was due to physical dependence, it was necessary to know the extent of direct barbiturate effect. This information is not available in the literature. Therefore, the proposed experiments were designed to provide this crucial information. These experiments will allow complete evaluation of the data already obtained in physically dependent animals so that the idea of decreased inhibitory function can be accepted or rejected as a primary mechanism underlying physical dependence.